The Neuropathology (NP) Core provides complete brain banking and neuropathology diagnostic services for the Pittsburgh ADRC with the goal of providing well-characterized tissues for research studies. Brain autopsies are performed on a 24-hour basis and the average post-mortem time over the past four years is approximately 6 hours. Over 150 frozen samples and CSF are banked. The brain is then fixed in 10% buffered formalin and blocks taken from 20 areas for microscopic evaluation. Stains used for evaluation include H&E, Congo Red, immunocytochemical (beta-A4 amyloid, tau, alpha-synuclein, and ubiquitin) and silver stains (Bielschowsky). Evaluation is performed using NIA-RI guidelines. Lewy Body pathology is assessed per the DLB consensus criteria of McKeith et al. Tissues and data are made available to investigators only after approval by the ADRC Executive Committee. During the last 5 years (1999-2003), the NP Core has evaluated a total of 323 cases. 121 of these were part of the ADRC cohort (90.1% of these were banked). 186 cases were associated with the ADRC, the ALS bank or were medical autopsies. Ten HIV and 6 CJD cases were also evaluated. Control brains are banked and characterized by identical protocols. The NP Core provides regular updates to the NACC MDS. The Core is also an active participant in local, national and international conferences. The core maintains a reference laboratory (including a Ar/Kr laser confocal microscope) for development of quantitative analyses. The Genetics Core has been combined with the Neuropathology Core. The Genetics Core maintains a repository of DNA and genotypes on all participants of the University of Pittsburgh ADRC. The aims of the Genetics Core are: 1) to collect and bank DNA from blood and brain tissues from all participants into the University of Pittsburgh ADRC. 2) to generate genotype data for the APOE polymorphisms in the coding (codons 28, 112, 158) and regulatory (-491 A/T, -427 T/C, -219 G/T, -186 G/T and +113 G/C) regions, and other new genetic risk markers associated with late-onset Alzheimer's disease from DNA obtained in Aim 1, and 3) to provide banked DNA and genotype data to the ADRC Data Registry Base and to ADRC affiliated R01 and pilot projects so that the DNA can be used for other genetic markers screening and genotype data can be used to assess the genetic risk for Alzheimer's disease.